Enzymatic Hydroxylations of sp³-Carbons

Abstract

Enzymatic hydroxylation of activated and nonactivated sp 3 -carbons attracts keen interest from the chemistry community as it is one of the most challenging tasks in organic synthesis. Nature provides a vast number of enzymes with an enormous catalytic versatility to fulfill this task. Given that those very different enzymes have a distinct specificity in substrate scope, selectivity, activity, stability, and catalytic cycle, it is interesting to outline similarities and differences. In this Review, we intend to delineate which enzymes possess considerable advantages within specific issues. Heterologous production, crystal structure availability, enzyme engineering potential, and substrate promiscuity are essential factors for the applicability of these biocatalysts.

Peroxide-Mediated Oxygenation of Organic Compounds by Fungal Peroxygenases

“…According to enzyme nomenclature, unspecific peroxygenases (UPOs, EC 1.11.2.1) belong to the sub-subclass of oxidoreductases that act ‘with H 2 O 2 as acceptor, one oxygen atom of which is incorporated into the product’ ( ; (accessed on 20 December 2021) [ 1 ]). They bear a cysteine-ligated heme in the active site (heme-thiolate proteins/HTP) and behave ‘promiscuously’ with respect to oxygen transfer reactions, i.e., one individual UPO protein may catalyze dozens of different oxyfunctionalizations in dependence on the geometry of its heme access channel and the structure of the particular substrate molecules [ 2 , 3 , 4 ]. The first UPO was discovered as an ‘untypical’ veratryl-alcohol-oxidizing haloperoxidase in the Black Poplar mushroom ( Agrocybe aegerita , nowadays Cyclocybe aegerita ) [ 5 ], a hardwood and leaf-litter-dwelling edible fungus belonging to the large basidiomycetous order of Agaricales (which typically form mushrooms and ‘toadstools’ as fruiting organs) [ 6 ].…”

Valorization of Small Alkanes by Biocatalytic Oxyfunctionalization

“…Metal‐oxo complexes dominate the chemical repertoire of C−H activating catalysts [7] . Amongst the bioavailable metals such as Fe, Cu, Mn, and Co especially iron‐oxo complexes are predominantly used by enzymatic systems for the functionalization of nonactivated C−H bonds as found in alkanes [8] . The vast diversity of Fe‐dependent oxygenases (enzymes inserting oxygen atoms into organic starting materials) can be divided into heme‐iron and nonheme‐iron complexes as prosthetic groups (Figure 2).…”

“…[7] Amongst the bioavailable metals such as Fe, Cu, Mn, and Co especially iron-oxo complexes are predominantly used by enzymatic systems for the functionalization of nonactivated CÀ H bonds as found in alkanes. [8] The vast diversity of Fe-dependent oxygenases (enzymes inserting oxygen atoms into organic starting materials) can be divided into heme-iron and nonheme-iron complexes as prosthetic groups (Figure 2). Monooxygenases utilize molecular oxygen as a source of the O-atom incorporated; for the reductive activation of O 2 , oxygenases rely on the supply with reducing equivalents.…”

Conversion of viridicatic acid to crustosic acid by cytochrome P450 enzyme-catalysed hydroxylation and spontaneous cyclisation

“…Cytochrome P450 enzymes largely contribute to the high structural diversity of natural products as they catalyse the oxidation of C-H groups into more active functional groups (Crešnar and Petric 2011 ). These P450-mediated functionalisation reactions of unactivated carbon skeletons significantly increase the reactivity and are therefore often essential to provide substrates for tailoring reactions, demonstrating the role of P450s as key enzymes in many biosynthetic pathways (Münch et al 2021 ).…”